Using a novel optical technique, polarization-gated spectroscopy, our group detected an early increase in blood supply (EIBS) prior to any morphological manifestation of colon carcinogenesis. The goal of this research plan is to extend previous work to enable a better understanding of the EIBS phenomenon. Developing an imaging based system will allow visualization of microvasculature changes beyond the capabilities of the current probe with single-point measurements. The project will utilize the azoxymethane (AOM) rat model of colon cancer to determine the biological mechanisms responsible for this increase in blood supply (neovascularization, vasodilation, and extravasation), and the optimal colonic depth to identify this effect. Future clinical applications will result from developing a novel imaging technique to detect this phenomenon. Initial designs of the imaging system will be guided through Monte Carlo simulations to determine the dependence of optical geometries on penetration depth. Contrast enhancement will be investigated for optimization through polarization gating and limited bandwidths or filtering. From these experiments, a prototype imaging system will be built and penetration depth validated on a series of tissue phantoms with tunable optical properties. Subsequently, the imaging technique will be refined and quantification of blood content, as well as roughness, homogeneity or other discriminating textures will be classified. Using the same animal model for validation studies, further refinement and image analysis will provide insight on specific differentiation between normal mucosa and the microvascular changes within the endoscopically-normal mucosa associated with carcinogenic events. This study will elucidate the biological mechanisms of EIBS, as well as explore the feasibility of imaging this phenomenon for more accurate detection and localization of colonic neoplasia. Accordingly, developing an imaging technique to explore visualization of superficial microcirculation will lead to an in vivo imaging application that would allow for accurately detecting structural changes of precancerous conditions from the endoscopically-normal tissue during a colonoscopy. Given the relative inexpensiveness of the technology and ease of use, this would be a clinically practical approach. If successful, depth-resolved imaging of colonic mucosa could foster the understanding of the origins of EIBS and possibly carcinogenesis, as well as improve polyp detection, providing a more reliable early detection method for colon cancer. PUBLIC HEALTH RELEVANCE: The objective of this project is to improve and extend the optical techniques developed by our lab for early detection of colon cancer. This requires design and implementation of a novel imaging technique capable of detecting blood supply, specifically pertaining to the superficial capillary network of the colon during the progression of cancer. Through optimization of the imaging system, visualization of these changes in vasculature can pave the road for clinical applications to improve cancer detection.